During surgical procedures, it is important to minimize disturbance of the environment of tissue and cells as much as possible. A traumatic change in the environment surrounding internal cells may, for example, lead to the destruction of such cells or the destruction of the function of such cells. The destruction of cell function may even lead to destruction of other cells which are dependent upon a proper functioning of the destroyed cells. Therefore, during surgical procedures such as, for example, intraocular surgery, it is very important that the exposed tissue be continuously irrigated with solutions which approximate natural body fluids. Such solutions are called "tissue irrigating solutions". One of the earliest tissue irrigating solutions for ophthalmic procedures was an isotonic saline. However, it was quickly recognized that the isotonic saline was not adequate as an ophthalmic irrigating solution because it resulted in endothelial cell swelling, cell damage, and consequent corneal clouding.
Alternatively, various electrolyte solutions have been proposed as tissue irrigating solutions, particularly in ophthalmic procedures, because such solutions more closely resemble the aqueous humor of the eye. The earliest electrolyte solution was known as Ringer's solution, which was a combination of sodium, calcium and potassium ions along with sodium lactate. Another solution intended for tissue irrigation is known as a balanced salt solution (referred to as "BSS") which contains the essential sodium, potassium, calcium, and magnesium salt ions along with an acetate-citrate buffer system. It was successful and was used almost exclusively until several years ago. Within the last 10-15 years, there has developed a tissue irrigating solution which is a combination of the Ringer solution along with glutathione and sodium bicarbonate. This is sometimes referred to GBR, and in recent years has become a recognized tissue irrigating solution, especially for ophthalmic procedures. When dextrose, sodium hydrogen phosphate (Na.sub.2 HPO.sub.4), and sometimes adenosine are added to GBR, there results a fortified or enhanced balanced salt solution (sometimes referred to as "BSS Plus"), which has heretofore proven to be very effective for intraocular surgery.
The problem with GBR solutions and particularly the fortified or enhanced balanced salt solution is that they do not exhibit long term stability. Because they must be mixed essentially at the operative site, it is difficult to control and maintain sterility. There are various reasons why GBR type solutions are not stable. First, bicarbonate and phosphate tend to precipitate in the presence of the magnesium and calcium ions. Therefore, once mixed, the sodium bicarbonate quickly loses its ability to act as a pumping agent for causing the endothelium to perform its fluid transport function of maintaining an outward fluid transport to the stromal layer, which results in damage to the cornea. Stated otherwise, the purpose of the bicarbonate is to act as a pump and, when mixed with the magnesium or calcium ions, it quickly loses its pumping action. A second reason why the GBR solutions are not stable is that bicarbonate decomposes at a pH of less than about 8 and becomes carbon dioxide which again causes the bicarbonate to fail to act as a chemical pump during the surgical procedure. Finally, the glutathione is unstable at a pH greater than about 5. Therefore, the glutathione cannot exist in a basic solution and the bicarbonate cannot exist for extended periods in an acid solution.
A solution to this problem has been offered in U.S. Pat. Nos. 4,443,432 and 4,550,022, both issued to Garabedian et al. According to these two patents, initially two solutions are prepared, a first, basic solution providing the bicarbonate and sodium phosphate, and a second, acidic solution which provides the calcium and magnesium ions, as well as the dextrose and glutathione. The solutions are packaged and stored separately and mixed within 24 hours of use.
While the resulting irrigating product as described the Garabedian et al technique has achieved some degree of acceptance and success, there are some limitations as a result thereof. First, the long-term stability and maintenance of acceptable pH values is difficult to achieve in accordance with the method and techniques described in the Garabedian et al patents. Second, in order to steam sterilize the first, basic solution, it is necessary to place the glutathione in the second, acidic package, because glutathione cannot stand steam sterilizing. Third, since the sodium bicarbonate is in the first package, the package must be glass which is subject to breakage, because it is difficult to maintain the stability of sodium bicarbonate in solution in a polymeric container. This occurs because sodium bicarbonate will not remain stable in a polypropylene bottle as a result of the transmission of vapors through the wall of the bottle.